HRD Testing of Ovarian Cancer in Routine Practice: What Are We Dealing With?

Assessment of homologous recombination deficiency (HRD) status is now essential for ovarian cancer patient management. The aim of our study was to analyze the influence of ethnic variations, tumor purity, and neoadjuvant chemotherapy (CT) on the determination of HRD scores as well as to evaluate fea...

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Main Authors: Tatiana Kekeeva, Yulia Andreeva, Alexander Tanas, Alexey Kalinkin, Svetlana Khokhlova, Tatiana Tikhomirova, Alexandra Tyulyandina, Anatoly Popov, Maria Kuzmenko, Mikhail Volkonsky, Natalia Chernorubashkina, Valeria Saevets, Vadim Dmitriev, Valentina Nechushkina, Olga Vedrova, Sergei Andreev, Sergey Kutsev, Vladimir Strelnikov
Format: Article
Language:English
Published: MDPI AG 2023-06-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/24/13/10497
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author Tatiana Kekeeva
Yulia Andreeva
Alexander Tanas
Alexey Kalinkin
Svetlana Khokhlova
Tatiana Tikhomirova
Alexandra Tyulyandina
Anatoly Popov
Maria Kuzmenko
Mikhail Volkonsky
Natalia Chernorubashkina
Valeria Saevets
Vadim Dmitriev
Valentina Nechushkina
Olga Vedrova
Sergei Andreev
Sergey Kutsev
Vladimir Strelnikov
author_facet Tatiana Kekeeva
Yulia Andreeva
Alexander Tanas
Alexey Kalinkin
Svetlana Khokhlova
Tatiana Tikhomirova
Alexandra Tyulyandina
Anatoly Popov
Maria Kuzmenko
Mikhail Volkonsky
Natalia Chernorubashkina
Valeria Saevets
Vadim Dmitriev
Valentina Nechushkina
Olga Vedrova
Sergei Andreev
Sergey Kutsev
Vladimir Strelnikov
author_sort Tatiana Kekeeva
collection DOAJ
description Assessment of homologous recombination deficiency (HRD) status is now essential for ovarian cancer patient management. The aim of our study was to analyze the influence of ethnic variations, tumor purity, and neoadjuvant chemotherapy (CT) on the determination of HRD scores as well as to evaluate feasibility of HRD testing with the Amoy HRD Focus Assay in routine clinical practice. The HRD status, including the <i>BRCA</i> status and genomic scar score (GSS), was analyzed in 452 ovarian cancer specimens. The successful rate of HRD testing was 86% (388/452). The <i>BRCA</i> mutational rate was 29% (114/388); 252 samples (65%) were classified as HRD-positive. Our data demonstrate the feasibility of internal HRD testing by the AmoyDx HRD Focus Panel for high-grade serous ovarian cancer (HGSOC), showing results similar to other methods. The HRD rate in the Russian population is very similar to those of other European populations, as is the <i>BRCA</i> mutation frequency. The most substantial contribution to HRD level diversity is testing criteria depending on intrahospital arrangements. The analysis shows that biallelic <i>BRCA</i> alterations had higher GSS compared with those with monoallelic inactivation, consistent with positive HRD status. The study indicates that grades 1–2 of the pathological response caused by chemotherapy affect HRD scores and suggests controlling for tumor purity of 40% or more as a critical factor for GSS measurement.
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spelling doaj.art-3682af6d9f4047ae80003204e2316d3c2023-11-18T16:39:07ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-06-0124131049710.3390/ijms241310497HRD Testing of Ovarian Cancer in Routine Practice: What Are We Dealing With?Tatiana Kekeeva0Yulia Andreeva1Alexander Tanas2Alexey Kalinkin3Svetlana Khokhlova4Tatiana Tikhomirova5Alexandra Tyulyandina6Anatoly Popov7Maria Kuzmenko8Mikhail Volkonsky9Natalia Chernorubashkina10Valeria Saevets11Vadim Dmitriev12Valentina Nechushkina13Olga Vedrova14Sergei Andreev15Sergey Kutsev16Vladimir Strelnikov17Laboratory of Epigenetics, Research Centre for Medical Genetics, Moskvorechie St., 1, 115522 Moscow, RussiaDepartment of Pathology, Russian Medical Academy of Continuing Professional Education, 125993 Moscow, RussiaLaboratory of Epigenetics, Research Centre for Medical Genetics, Moskvorechie St., 1, 115522 Moscow, RussiaLaboratory of Epigenetics, Research Centre for Medical Genetics, Moskvorechie St., 1, 115522 Moscow, RussiaOncological Department of Medical Treatment, National Medical Research Center for Obstetrics, Gynecology and Perinatology Named after V. I. Kulakov, 117997 Moscow, RussiaN.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia, 115478 Moscow, RussiaN.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia, 115478 Moscow, RussiaNational Medical Research Center of Surgery Named after A. Vishnevsky, Department of Antitumor Drug Therapy, 117997 Moscow, RussiaDepartment of Oncology, Radiology and Radiotherapy, Tyumen State Medical University, 625023 Tyumen, RussiaDay Hospital No. 1, Moscow Municipal Oncological Hospital No. 62, 143423 Moscow, RussiaDepartment of Surgical Methods of Treatment No. 9, State Budgetary Healthcare Institution Regional Oncological Dispensary, 664035 Irkutsk, RussiaGynecological Oncology Department, Chelyabinsk Regional Clinical Centre for Oncology and Nuclear Medicine, 454087 Chelyabinsk, RussiaDepartment of Theoretical Surgery, Belgorod National Research University, 308015 Belgorod, RussiaDepartment of Oncology, Diagnostic Radiology and Radiotherapy, Privolzhsky Research Medical University, 603005 Nizhniy Novgorod, RussiaAstrazeneca Pharmaceuticals LLC, 123112 Moscow, RussiaAstrazeneca Pharmaceuticals LLC, 123112 Moscow, RussiaLaboratory of Epigenetics, Research Centre for Medical Genetics, Moskvorechie St., 1, 115522 Moscow, RussiaLaboratory of Epigenetics, Research Centre for Medical Genetics, Moskvorechie St., 1, 115522 Moscow, RussiaAssessment of homologous recombination deficiency (HRD) status is now essential for ovarian cancer patient management. The aim of our study was to analyze the influence of ethnic variations, tumor purity, and neoadjuvant chemotherapy (CT) on the determination of HRD scores as well as to evaluate feasibility of HRD testing with the Amoy HRD Focus Assay in routine clinical practice. The HRD status, including the <i>BRCA</i> status and genomic scar score (GSS), was analyzed in 452 ovarian cancer specimens. The successful rate of HRD testing was 86% (388/452). The <i>BRCA</i> mutational rate was 29% (114/388); 252 samples (65%) were classified as HRD-positive. Our data demonstrate the feasibility of internal HRD testing by the AmoyDx HRD Focus Panel for high-grade serous ovarian cancer (HGSOC), showing results similar to other methods. The HRD rate in the Russian population is very similar to those of other European populations, as is the <i>BRCA</i> mutation frequency. The most substantial contribution to HRD level diversity is testing criteria depending on intrahospital arrangements. The analysis shows that biallelic <i>BRCA</i> alterations had higher GSS compared with those with monoallelic inactivation, consistent with positive HRD status. The study indicates that grades 1–2 of the pathological response caused by chemotherapy affect HRD scores and suggests controlling for tumor purity of 40% or more as a critical factor for GSS measurement.https://www.mdpi.com/1422-0067/24/13/10497homologous recombination deficiency<i>BRCA</i> mutationgenomic instability scoretumor puritypathological response
spellingShingle Tatiana Kekeeva
Yulia Andreeva
Alexander Tanas
Alexey Kalinkin
Svetlana Khokhlova
Tatiana Tikhomirova
Alexandra Tyulyandina
Anatoly Popov
Maria Kuzmenko
Mikhail Volkonsky
Natalia Chernorubashkina
Valeria Saevets
Vadim Dmitriev
Valentina Nechushkina
Olga Vedrova
Sergei Andreev
Sergey Kutsev
Vladimir Strelnikov
HRD Testing of Ovarian Cancer in Routine Practice: What Are We Dealing With?
International Journal of Molecular Sciences
homologous recombination deficiency
<i>BRCA</i> mutation
genomic instability score
tumor purity
pathological response
title HRD Testing of Ovarian Cancer in Routine Practice: What Are We Dealing With?
title_full HRD Testing of Ovarian Cancer in Routine Practice: What Are We Dealing With?
title_fullStr HRD Testing of Ovarian Cancer in Routine Practice: What Are We Dealing With?
title_full_unstemmed HRD Testing of Ovarian Cancer in Routine Practice: What Are We Dealing With?
title_short HRD Testing of Ovarian Cancer in Routine Practice: What Are We Dealing With?
title_sort hrd testing of ovarian cancer in routine practice what are we dealing with
topic homologous recombination deficiency
<i>BRCA</i> mutation
genomic instability score
tumor purity
pathological response
url https://www.mdpi.com/1422-0067/24/13/10497
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